We plan to continue our studies on the relatrive importance of the covalent binding of CCl4 reactive metabolites to cell constituents and lipid peroxidation in CC14-induced liver injury. We also plan to study how alterations initiated by any of both processes at the endoplasmic reticulum (ER) propagate to the other organelles. We plan to analyze the possibility of explaining that process by looking for multiple sites of CCl4 activation in the cell; by a participation of CCl4-induced blockade of synthesis of proteins needed in organelles, other than the ER and by the export of altered proteins and phospholipids produced in the ER to other organelles. We plant to explore the role of protein and phospholipid syntheis and degradation in addition to that of covalent binding, in the process followed by a critical irreversible step leading to cell death. We also plan to rest the hypothesis that early calcium accumulation sparks this last irreversible step. We also plan to continue with our studies on themechanism of CCl4 liver tumor induction by analyzing further the alterations in DNA occuring during CCl4 administration. We plan to develop effective treatments of possible practical therapeutic value against chemically induced hepatotoxicity; based on our previous findings in protective effects of several aminoacids. The health-related implications of our studies are critical, because CCl4 hepatotoxicity is a model system for many other chemicals acting on liver and other organs. The development of effective treatments depends on answering these questions. The tools of chemistry and biology to be employed might solve these questions. These studies on CCl4 liver tumor induction might have relevance to the problem of CCl4 contamination of water supplies of metropolitan areas of the United States of America.